Community-level bystander treatment and outcomes for witnessed out-of-hospital cardiac arrest in the state of Connecticut.

Background: Prior reports have demonstrated underutilization of bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use in patients with witnessed out-of-hospital cardiac arrest (OHCA) in Connecticut. This study aimed to identify community-level risk factors that contribute to low rates of bystander intervention to improve statewide OHCA outcomes. Methods: We analyzed 2,789 adult patients with witnessed, non-traumatic OHCA submitted to the Connecticut Cardiac Arrest Registry to Enhance Survival (CARES) between 2013-2022. Patients were grouped by zip code, and associated municipal characteristics were acquired from 2022 United States Census Bureau data. Use of bystander CPR, attempted bystander AED defibrillation, and patient survival with favorable neurological function were determined for 19 of the 20 most populous cities and towns. Pearson correlation tests and linear regression were used to determine associations between OHCA treatment and outcomes with population size, racial/ethnic demographics, language use, income, and educational level. Results: Bystander CPR was lower in municipalities with population size > 100,000 and in communities where > 40% of residents are non-English-speaking. AED use was also lower in these municipalities, as well as those with per capita incomes < $40,000 or > 1/3 Hispanic residents. Communities with populations > 100,000, > 40% non-English-speaking, per capita income < $40,000, and > 1/3 Hispanic residents were all associated with lower survival rates. Conclusions: OHCA pre-hospital treatment and outcomes vary significantly by municipality in Connecticut. Community outcomes might be improved by specifically targeting urban population centers and Hispanic communities with culturally sensitive, low, or no-cost CPR and AED educational programs, using instructional languages other than English.

Glioblastoma Spheroid Invasion through Soft, Brain-Like Matrices Depends on Hyaluronic Acid-CD44 Interactions.

Increased secretion of hyaluronic acid (HA), a glycosaminoglycan abundant in the brain extracellular matrix (ECM), correlates with worse clinical outcomes for glioblastoma (GBM) patients. GBM cells aggressively invade the brain parenchyma while encountering spatiotemporal changes in their local ECM, including HA concentration. To investigate how varying HA concentrations affect GBM invasion, patient-derived GBM cells are cultured within a soft, 3D matrix in which HA concentration is precisely varied and cell migration observed. Data demonstrate that HA concentration can determine the invasive activity of patient-derived GBM cells in a biphasic and highly sensitive manner, where the absolute concentration of HA at which cell migration peaked is specific to each patient-derived line. Furthermore, evidence that this response relies on phosphorylated ezrin, which interacts with the intracellular domain of HA-engaged CD44 to effectively link the actin cytoskeleton to the local ECM is provided. Overall, this study highlights CD44-HA binding as a major mediator of GBM cell migration that acts independently of integrins and focal adhesion complexes and suggests that targeting HA-CD44-ezrin interactions represents a promising therapeutic strategy to prevent tumor cell invasion in the brain.